Single-cell sequencing uncovers disrupted stromal-macrophage communication as a driver of intrauterine adhesion progression
Intrauterine adhesions (IUA), characterized by endometrial fibrosis, pose a serious threat to women's reproductive health, yet their molecular mechanisms remain poorly understood. Here, we use single-cell RNA sequencing (scRNA-seq) to profile 139,395 single cells from nine individuals in the proliferative phase. We identify seven stromal and five macrophage subsets, revealing increased immune cell infiltration and a profibrotic shift in macrophage states. Immunohistochemistry confirms elevated CD68<sup>+</sup> macrophages and higher expression of S100A8, CCL2, CCL5, and SPP1 in IUA tissues. In vitro, macrophage-derived CCL5 and SPP1 promote fibroblast-to-myofibroblast transition. Trajectory and ligand-receptor analysis highlight profibrotic macrophage lineages and TGF-β signaling as a key driver of fibrosis. Integration with secretory-phase single-cell data provides a comprehensive view of IUA across menstrual phases. These findings uncover a pivotal role for macrophage-stromal interactions in IUA progression and suggest potential therapeutic targets.
Authors
- Lujuan Rong (ORCID: https://orcid.org/0009-0000-0583-3106)
- Ran Zhu (ORCID: https://orcid.org/0000-0003-0874-9369)
- Erbo Dong (ORCID: https://orcid.org/0000-0002-0654-0660)
- Xiaozhuo Li
- Tianqing Li (ORCID: https://orcid.org/0000-0001-7453-0184)
- Tingwei Chen (ORCID: https://orcid.org/0000-0003-4840-8534)
- Jiwen Tian
- Xiaomei Wu (ORCID: https://orcid.org/0000-0002-7425-8755)
- Yan He (ORCID: https://orcid.org/0000-0001-7928-2677)
- Yu Yin (ORCID: https://orcid.org/0000-0001-6040-6115)
- Zhengli Zhou
- Jingxue Zhao
- Ting Liu (ORCID: https://orcid.org/0000-0001-8908-9483)
- Bo Zhang (ORCID: https://orcid.org/0009-0000-7452-5510)
- Naixue Yang (ORCID: https://orcid.org/0000-0002-0705-7611)
- Jie Yang
- Wenshu Zhou (ORCID: https://orcid.org/0009-0004-8015-6992)
Institutions
- Kunming University of Science and Technology (CN)
- Kunming Medical University (CN)
- First People's Hospital of Yunnan Province (CN)
- The First Hospital of Kunming (CN)
- First Affiliated Hospital of Kunming Medical University (CN)
- Yunnan Yingmao Biotechnology (China) (CN)
Publication Details
- Journal
- Communications Biology
- Published
- 2025-08-11
- DOI
- https://doi.org/10.1038/s42003-025-08634-3
- Citations
- 3
- Primary Topic
- Renal and related cancers
- Type
- article
- Field-Weighted Citation Impact
- 2.42
Funders
- National Natural Science Foundation of China
- Kunming Medical University
- Natural Science Foundation of Yunnan Province
- Kunming University of Science and Technology
- Yunnan Provincial Department of Education
- National Key Research and Development Program of China